PROJECT SUMMARY Evidence suggests that exposure to Superfund chemicals contributes to adverse pregnancy outcomes (APOs), including preterm birth (PTB). Rates of PTB and infant mortality in Puerto Rico (PR) are among the highest of all US states and territories. There are 18 Superfund sites in PR, and evidence of contamination of the drinking water is extensive. Moreover, extreme weather events (hurricanes, flooding) may result in elevated exposures to Superfund chemicals. The PROTECT center has brought together researchers from Northeastern University, the University of Puerto Rico, University of Georgia, and the University of Michigan to provide much needed understanding of the relationship and the mechanisms by which exposure to suspect chemicals contribute to APOs, and to develop new methods to reduce risk of exposure in PR and beyond. To do this, PROTECT uses a source-to-outcome structure, integrating epidemiological (Project 1), toxicological (Project 2), fate and transport (Project 3), and remediation (Project 4) studies, a unified sampling infrastructure, a centralized indexed data repository, and a sophisticated data management system. Since its inception in 2010, PROTECT has built detailed and extensive data sets on environmental conditions and prenatal conditions of 1457 pregnant mothers (exposure, socioeconomic and health data?close to 3000 data points per participant), yielding a cohort of 1210 live births in northern PR. In the renewal, PROTECT will recruit and follow an additional 1000 study participants, yielding a cohort of 800+ live births for an ultimate total cohort of 2000+ completed live births. PROTECT has documented significant contamination of northern PR drinking water and has found compelling preliminary epidemiologic and mechanistic toxicology associations between Superfund chemicals and APOs. PROTECT research has focused on chlorinated volatile organic compounds and phthalates and their role in PTB. The PROTECT renewal will broaden its scope, employing a data-driven approach to study and reduce the impact of exposure to mixtures of suspect chemicals from Superfund sites in karst regions on APOs in Puerto Rico?s underserved, highly-exposed population. Target chemicals will be expanded to include metals, pesticides, and polycyclic aromatic hydrocarbons. We will investigate the impacts of extreme weather events on contaminant transport and exposure, and new water treatment technologies will be developed for portable and robust water treatment systems. The PROTECT renewal will also focus on oxidative stress as an underlying biological pathway by which contaminant exposure can lead to APOs. New statistical methods and data mining, machine learning, and visualization tools will be developed to allow PROTECT researchers to analyze our datasets. PROTECT will employ innovative approaches to engage and educate the community, involve study participants, report- back data, and communicate with stakeholders. A broad suite of training and professional activities will be provided to trainees, individually tailored to the trainees? needs and goals.